scholarly journals Cardiovascular and skeletal muscle health with lifelong exercise

2018 ◽  
Vol 125 (5) ◽  
pp. 1636-1645 ◽  
Author(s):  
Kevin J. Gries ◽  
Ulrika Raue ◽  
Ryan K. Perkins ◽  
Kaleen M. Lavin ◽  
Brittany S. Overstreet ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Aerobic Exercise ◽  
Muscle Biopsy ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Metabolic Phenotype ◽  
Vastus Lateralis Muscle ◽  
Metabolic Fitness ◽  
Lifelong Exercise

The purpose of this study was to examine the effects of aerobic lifelong exercise (LLE) on maximum oxygen consumption (V̇o2max) and skeletal muscle metabolic fitness in trained women ( n = 7, 72 ± 2 yr) and men ( n = 21, 74 ± 1 yr) and compare them to old, healthy nonexercisers (OH; women: n = 10, 75 ± 1 yr; men: n = 10, 75 ± 1 yr) and young exercisers (YE; women: n = 10, 25 ± 1 yr; men: n = 10, 25 ± 1 yr). LLE men were further subdivided based on intensity of lifelong exercise and competitive status into performance (LLE-P, n = 14) and fitness (LLE-F, n = 7). On average, LLE exercised 5 day/wk for 7 h/wk over the past 52 ± 1 yr. Each subject performed a maximal cycle test to assess V̇o2maxand had a vastus lateralis muscle biopsy to examine capillarization and metabolic enzymes [citrate synthase, β-hydroxyacyl-CoA dehydrogenase (β-HAD), and glycogen phosphorylase]. V̇o2maxhad a hierarchical pattern (YE > LLE > OH, P < 0.05) for women (44 ± 2 > 26 ± 2 > 18 ± 1 ml·kg−1·min−1) and men (53 ± 3 > 34 ± 1 > 22 ± 1 ml·kg−1·min−1) and was greater ( P < 0.05) in LLE-P (38 ± 1 ml·kg−1·min−1) than LLE-F (27 ± 2 ml·kg−1·min−1). LLE men regardless of intensity and women had similar capillarization and aerobic enzyme activity (citrate synthase and β-HAD) as YE, which were 20%–90% greater ( P < 0.05) than OH. In summary, these data show a substantial V̇o2maxbenefit with LLE that tracked similarly between the sexes, with further enhancement in performance-trained men. For skeletal muscle, 50+ years of aerobic exercise fully preserved capillarization and aerobic enzymes, regardless of intensity. These data suggest that skeletal muscle metabolic fitness may be easier to maintain with lifelong aerobic exercise than more central aspects of the cardiovascular system.NEW & NOTEWORTHY Lifelong exercise (LLE) is a relatively new and evolving area of study with information especially limited in women and individuals with varying exercise intensity habits. These data show a substantial maximal oxygen consumption benefit with LLE that tracked similarly between the sexes. Our findings contribute to the very limited skeletal muscle biopsy data from LLE women (>70 yr), and similar to men, revealed a preserved metabolic phenotype comparable to young exercisers.

Muscle blood flow during exercise in sedentary and trained hypothyroid rats

1995 ◽  
Vol 269 (6) ◽  
pp. H1949-H1954 ◽  
Author(s):  
R. M. McAllister ◽  
M. D. Delp ◽  
K. A. Thayer ◽  
M. H. Laughlin
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Muscle Blood Flow ◽  
Treadmill Running ◽  
Exercise Intolerance ◽  
Vastus Lateralis Muscle ◽  
Blood Flows ◽  
Vastus Intermedius

Hypothyroidism is characterized by exercise intolerance. We hypothesized that active muscle blood flow during in vivo exercise is inadequate in the hypothyroid state. Additionally, we hypothesized that endurance exercise training would restore normal blood flow during acute exercise. To test these hypotheses, rats were made hypothyroid (Hypo) over 3-4 mo with propylthiouracil. A subset of Hypo rats was trained (THypo) on a treadmill at 30 m/min (15% grade) for 60 min/day 5 days/wk over 10-15 wk. Hypothyroidism was evidenced by approximately 80% reductions in plasma triiodothyronine levels in Hypo and THypo and by 40-50% reductions in citrate synthase activities in high oxidative muscles in Hypo compared with euthyroid (Eut) rats. Training efficacy was indicated by increased (25-100%) citrate synthase activities in muscles of THypo vs. Hypo. Regional blood flows were determined by the radiolabeled microsphere method before exercise and at 1-2 min of treadmill running at 15 m/min (0% grade). Preexercise muscle blood flows were generally similar among groups. During exercise, however, flows were lower in Hypo than in Eut for high oxidative muscles such as the red section of vastus lateralis [277 +/- 24 and 153 +/- 13 (SE) ml.min-1.100 g-1 for Eut and Hypo, respectively; P < 0.01] and vastus intermedius (317 +/- 32 and 187 +/- 20 ml.min-1.100 g-1 for Eut and Hypo, respectively; P < 0.01) muscles. Training (THypo) did not normalize these flows (168 +/- 24 and 181 +/- 24 ml.min-1.100 g-1 for red section of vastus lateralis and vastus intermedius muscles, respectively). Blood flows to low oxidative muscle, such as the white section of vastus lateralis muscle, were similar among groups (21 +/- 5, 25 +/- 4, and 34 +/- 7 ml.min-1.100 g-1 for Eut, Hypo, and THypo, respectively; P = NS). These findings indicate that hypothyroidism is associated with reduced blood flow to skeletal muscle during exercise, suggesting that impaired delivery of nutrients to and/or removal of metabolites from skeletal muscle contributes to the poor exercise tolerance characteristic of hypothyroidism.

scholarly journals Transcriptomic Signatures and Upstream Regulation in Human Skeletal Muscle Adapted to Disuse and Aerobic Exercise

2021 ◽  
Vol 22 (3) ◽  
pp. 1208
Author(s):  
Pavel A. Makhnovskii ◽  
Roman O. Bokov ◽  
Fedor A. Kolpakov ◽  
Daniil V. Popov
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Aerobic Exercise ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Biological Effects ◽  
Vastus Lateralis ◽  
Regulation Of Gene Expression ◽  
Vastus Lateralis Muscle ◽  
Healthy Humans

Inactivity is associated with the development of numerous disorders. Regular aerobic exercise is broadly used as a key intervention to prevent and treat these pathological conditions. In our meta-analysis we aimed to identify and compare (i) the transcriptomic signatures related to disuse, regular and acute aerobic exercise in human skeletal muscle and (ii) the biological effects and transcription factors associated with these transcriptomic changes. A standardized workflow with robust cut-off criteria was used to analyze 27 transcriptomic datasets for the vastus lateralis muscle of healthy humans subjected to disuse, regular and acute aerobic exercise. We evaluated the role of transcriptional regulation in the phenotypic changes described in the literature. The responses to chronic interventions (disuse and regular training) partially correspond to the phenotypic effects. Acute exercise induces changes that are mainly related to the regulation of gene expression, including a strong enrichment of several transcription factors (most of which are related to the ATF/CREB/AP-1 superfamily) and a massive increase in the expression levels of genes encoding transcription factors and co-activators. Overall, the adaptation strategies of skeletal muscle to decreased and increased levels of physical activity differ in direction and demonstrate qualitative differences that are closely associated with the activation of different sets of transcription factors.

scholarly journals New records in aerobic power among octogenarian lifelong endurance athletes

2013 ◽  
Vol 114 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Scott Trappe ◽  
Erik Hayes ◽  
Andrew Galpin ◽  
Leonard Kaminsky ◽  
Bozena Jemiolo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Aerobic Capacity ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Endurance Athletes ◽  
Whole Body ◽  
Oxidative Enzymes ◽  
Vastus Lateralis Muscle ◽  
Peroxisome Proliferator ◽  
Mrna Targets

We examined whole body aerobic capacity and myocellular markers of oxidative metabolism in lifelong endurance athletes [ n = 9, 81 ± 1 yr, 68 ± 3 kg, body mass index (BMI) = 23 ± 1 kg/m2] and age-matched, healthy, untrained men ( n = 6; 82 ± 1 y, 77 ± 5 kg, BMI = 26 ± 1 kg/m2). The endurance athletes were cross-country skiers, including a former Olympic champion and several national/regional champions, with a history of aerobic exercise and participation in endurance events throughout their lives. Each subject performed a maximal cycle test to assess aerobic capacity (V̇o2max). Subjects had a resting vastus lateralis muscle biopsy to assess oxidative enzymes (citrate synthase and βHAD) and molecular (mRNA) targets associated with mitochondrial biogenesis [peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and mitochondrial transcription factor A (Tfam)]. The octogenarian athletes had a higher ( P < 0.05) absolute (2.6 ± 0.1 vs. 1.6 ± 0.1 l/min) and relative (38 ± 1 vs. 21 ± 1 ml·kg−1·min−1) V̇o2max, ventilation (79 ± 3 vs. 64 ± 7 l/min), heart rate (160 ± 5 vs. 146 ± 8 beats per minute), and final workload (182 ± 4 vs. 131 ± 14 W). Skeletal muscle oxidative enzymes were 54% (citrate synthase) and 42% (βHAD) higher ( P < 0.05) in the octogenarian athletes. Likewise, basal PGC-1α and Tfam mRNA were 135% and 80% greater ( P < 0.05) in the octogenarian athletes. To our knowledge, the V̇o2max of the lifelong endurance athletes is the highest recorded in humans >80 yr of age and comparable to nonendurance trained men 40 years younger. The superior cardiovascular and skeletal muscle health profile of the octogenarian athletes provides a large functional reserve above the aerobic frailty threshold and is associated with lower risk for disability and mortality.

scholarly journals Impaired exercise training-induced muscle fiber hypertrophy and Akt/mTOR pathway activation in hypoxemic patients with COPD

2015 ◽  
Vol 118 (8) ◽  
pp. 1040-1049 ◽  
Author(s):  
Frédéric Costes ◽  
Harry Gosker ◽  
Léonard Feasson ◽  
Marine Desgeorges ◽  
Marco Kelders ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Muscle Fiber ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
C2c12 Myotubes ◽  
Chronic Obstructive ◽  
Vastus Lateralis Muscle ◽  
Cross Sectional ◽  
Gsk 3Β

Exercise training (ExTr) is largely used to improve functional capacity in patients with chronic obstructive pulmonary disease (COPD). However, ExTr only partially restores muscle function in patients with COPD, suggesting that confounding factors may limit the efficiency of ExTr. In the present study, we hypothesized that skeletal muscle adaptations triggered by ExTr could be compromised in hypoxemic patients with COPD. Vastus lateralis muscle biopsies were obtained from patients with COPD who were either normoxemic ( n = 15, resting arterial Po2 = 68.5 ± 1.5 mmHg) or hypoxemic ( n = 8, resting arterial Po2 = 57.0 ± 1.0 mmHg) before and after a 2-mo ExTr program. ExTr induced a significant increase in exercise capacity both in normoxemic and hypoxemic patients with COPD. However, ExTr increased citrate synthase and lactate dehydrogenase enzyme activities only in skeletal muscle of normoxemic patients. Similarly, muscle fiber cross-sectional area and capillary-to-fiber ratio were increased only in patients who were normoxemic. Expression of atrogenes (MuRF1, MAFbx/Atrogin-1) and autophagy-related genes (Beclin, LC3, Bnip, Gabarapl) remained unchanged in both groups. Phosphorylation of Akt (Ser473), GSK-3β (Ser9), and p70S6k (Thr389) was nonsignificantly increased in normoxemic patients in response to ExTr, but it was significantly decreased in hypoxemic patients. We further showed on C2C12 myotubes that hypoxia completely prevented insulin-like growth factor-1-induced phosphorylation of Akt, GSK-3β, and p70S6K. Together, our observations suggest a role for hypoxemia in the adaptive response of skeletal muscle of patients with COPD in an ExTr program.

Skeletal muscle GLUT-4 and glucose uptake during exercise in humans

1994 ◽  
Vol 77 (3) ◽  
pp. 1565-1568 ◽  
Author(s):  
G. McConell ◽  
M. McCoy ◽  
J. Proietto ◽  
M. Hargreaves
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Glucose Uptake ◽  
Muscle Glycogen ◽  
Protein Level ◽  
Glycogen Content ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Muscle Glycogen Content ◽  
Glut 4

The present study examined the relationship between total skeletal muscle GLUT-4 protein level and glucose uptake during exercise. Eight active non-endurance-trained men cycled at 72 +/- 1% peak pulmonary oxygen consumption for 40 min, with rates of glucose appearance and disappearance (Rd) determined by utilizing a primed continuous infusion of [3–3H]glucose commencing 2 h before exercise. Muscle glycogen content and utilization, citrate synthase activity, and total GLUT-4 protein were measured on muscle biopsy samples obtained from the vastus lateralis. A direct relationship existed between preexercise muscle glycogen content and glycogen utilization during exercise (r = 0.76, P < 0.05). Citrate synthase activity and glucose Rd at the end of exercise averaged 21.9 +/- 3.0 mumol.min-1.g-1 and 27.3 +/- 2.5 mumol.kg-1.min-1, respectively. There was a direct correlation between citrate synthase activity and GLUT-4 protein (r = 0.78, P < 0.05); however, at the end of exercise, glucose Rd was inversely related to both GLUT-4 (r = -0.89, P < 0.01) and citrate synthase activity (r = -0.72, P < 0.05). Plasma insulin, which decreased during exercise, was not related to glucose Rd. In conclusion, glucose uptake during 40 min of exercise at 72% peak pulmonary oxygen consumption was inversely related to the total muscle GLUT-4 protein level. This suggests that factors other than the total GLUT-4 protein level are important in the regulation of glucose uptake during exercise.

scholarly journals Metabolic phenotype of skeletal muscle in early critical illness

Thorax ◽  
2018 ◽  
Vol 73 (10) ◽  
pp. 926-935 ◽  
Author(s):  
Zudin A Puthucheary ◽  
Ronan Astin ◽  
Mark J W Mcphail ◽  
Saima Saeed ◽  
Yasmin Pasha ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Critical Illness ◽  
Muscle Mass ◽  
Mitochondrial Biogenesis ◽  
Vastus Lateralis ◽  
Metabolic Phenotype ◽  
Tumour Necrosis Factor Receptor ◽  
Vastus Lateralis Muscle ◽  
Atp Content ◽  
Mitochondrial Dna Copy Number

ObjectivesTo characterise the sketetal muscle metabolic phenotype during early critical illness.MethodsVastus lateralis muscle biopsies and serum samples (days 1 and 7) were obtained from 63 intensive care patients (59% male, 54.7±18.0 years, Acute Physiology and Chronic Health Evaluation II score 23.5±6.5).Measurements and main resultsFrom day 1 to 7, there was a reduction in mitochondrial beta-oxidation enzyme concentrations, mitochondrial biogenesis markers (PGC1α messenger mRNA expression (−27.4CN (95% CI −123.9 to 14.3); n=23; p=0.025) and mitochondrial DNA copy number (−1859CN (IQR −5557–1325); n=35; p=0.032). Intramuscular ATP content was reduced compared tocompared with controls on day 1 (17.7mmol/kg /dry weight (dw) (95% CI 15.3 to 20.0) vs. 21.7 mmol/kg /dw (95% CI 20.4 to 22.9); p<0.001) and decreased over 7 days (−4.8 mmol/kg dw (IQR −8.0–1.2); n=33; p=0.001). In addition, the ratio of phosphorylated:total AMP-K (the bioenergetic sensor) increased (0.52 (IQR −0.09–2.6); n=31; p<0.001). There was an increase in intramuscular phosphocholine (847.2AU (IQR 232.5–1672); n=15; p=0.022), intramuscular tumour necrosis factor receptor 1 (0.66 µg (IQR −0.44–3.33); n=29; p=0.041) and IL-10 (13.6 ng (IQR 3.4–39.0); n=29; p=0.004). Serum adiponectin (10.3 µg (95% CI 6.8 to 13.7); p<0.001) and ghrelin (16.0 ng/mL (IQR −7–100); p=0.028) increased. Network analysis revealed a close and direct relationship between bioenergetic impairment and reduction in muscle mass and between intramuscular inflammation and impaired anabolic signaling. ATP content and muscle mass were unrelated to lipids delivered.ConclusionsDecreased mitochondrial biogenesis and dysregulated lipid oxidation contribute to compromised skeletal muscle bioenergetic status. In addition, intramuscular inflammation was associated with impaired anabolic recovery with lipid delivery observed as bioenergetically inert. Future clinical work will focus on these key areas to ameliorate acute skeletal muscle wasting.Trial registration numberNCT01106300.

scholarly journals Human skeletal muscle carnitine palmitoyltransferase I activity determined in isolated intact mitochondria

1998 ◽  
Vol 85 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Phanélie M. Berthon ◽  
Richard A. Howlett ◽  
George J. F. Heigenhauser ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Maximal Oxygen Consumption ◽  
Carnitine Palmitoyltransferase ◽  
Vastus Lateralis Muscle ◽  
Malonyl Coa ◽  
Human Muscle Biopsy ◽  
Carnitine Palmitoyltransferase I ◽  
Cpt I

This study was designed to compare the activity of skeletal muscle carnitine palmitoyltransferase I (CPT I) in trained and inactive men ( n = 14) and women ( n = 12). CPT I activity was measured in intact mitochondria, isolated from needle biopsy vastus lateralis muscle samples (∼60 mg). The variability of CPT I activity determined on two biopsy samples from the same leg on the same day was 4.4, whereas it was 7.0% on two biopsy samples from the same leg on different days. The method was sensitive to the CPT I inhibitor malonyl-CoA (88% inhibition) and therefore specific for CPT I activity. The mean CPT I activity for all 26 subjects was 141.1 ± 10.6 μmol ⋅ min−1 ⋅ kg wet muscle (wm)−1 and was not different when all men vs. all women (140.5 ± 15.7 and 142.2 ± 14.5 μmol ⋅ min−1 ⋅ kg wm−1, respectively) were compared. However, CPT I activity was significantly higher in trained vs. inactive subjects for both men (176.2 ± 21.1 vs. 104.1 ± 13.6 μmol ⋅ min−1 ⋅ kg wm−1) and women (167.6 ± 14.1 vs. 91.2 ± 9.5 μmol ⋅ min−1 ⋅ kg wm−1). CPT I activity was also significantly correlated with citrate synthase activity (all subjects, r = 0.76) and maximal oxygen consumption expressed in milliliters per kilogram per minute (all subjects, r = 0.69). The results of this study suggest that CPT I activity can be accurately and reliably measured in intact mitochondria isolated from human muscle biopsy samples. CPT I activity was not affected by gender, and higher activities in aerobically trained subjects appeared to be the result of increased mitochondrial content in both men and women.

Effect of training and detraining on skeletal muscle glucose transporter (GLUT4) content in rats

1992 ◽  
Vol 70 (9) ◽  
pp. 1286-1290 ◽  
Author(s):  
P. D. Neufer ◽  
M. H. Shinebarger ◽  
G. L. Dohm
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Glucose Transporter ◽  
Citrate Synthase ◽  
Treadmill Exercise ◽  
Vastus Lateralis ◽  
Vastus Lateralis Muscle ◽  
Transporter Protein ◽  
Lateralis Muscle ◽  
Training And Detraining

The aim of the present study was to examine the effects of treadmill exercise training and detraining on the skeletal muscle fiber type specific expression of the insulin-regulated glucose transporter protein (GLUT4) in rats. GLUT4 protein content was determined by Western and dot-blot analysis, using a polyclonal antibody raised against the carboxy-terminal peptide. Rats were sacrificed 24 h after the last training session. There were no significant changes in muscle GLUT4 after 1 day or 1 week of training. Six weeks of training increased GLUT4 protein content 1.4- to 1.7-fold (p < 0.05) over controls in the soleus and red vastus lateralis, whereas no significant change was evident in the white vastus lateralis muscle. GLUT4 protein content in both soleus and red vastus lateralis muscle returned to near control values after 7 days of detraining. Similar to GLUT4, citrate synthase activity showed no change after 1 day or 1 week of training, increased 1.8-fold over controls after 6 weeks of training, but returned to control values after 7 days detraining. These findings demonstrate that muscle GLUT4 protein is increased in rats with as little as 6 weeks of treadmill exercise training but that the adaptation is lost within 1 week of detraining. It is suggested that expression of the GLUT4 protein is coordinated with the well-documented adaptations in oxidative enzyme activity with endurance training and detraining.Key words: insulin-regulated glucose transporter protein, citrate synthase.

Time course of responses of human skeletal muscle to oxidative stress induced by nondamaging exercise

2001 ◽  
Vol 90 (3) ◽  
pp. 1031-1035 ◽  
Author(s):  
Muna Khassaf ◽  
Robert B. Child ◽  
Anne McArdle ◽  
David A. Brodie ◽  
Cristian Esanu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Superoxide Dismutase ◽  
Aerobic Exercise ◽  
Time Course ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Exercise Bout ◽  
Superoxide Dismutase Activity ◽  
Vastus Lateralis Muscle ◽  
Shock Proteins

Previous studies in animals have demonstrated that a single period of aerobic exercise induces a rise in the skeletal muscle activity of the antioxidant enzymes superoxide dismutase and catalase and an increase in the muscle content of heat shock proteins (HSPs). The purpose of this study was to examine the time course of response of human skeletal muscle superoxide dismutase and catalase activities and the content of HSP60 and HSP70 after a period of exhaustive, nondamaging aerobic exercise. Seven volunteers undertook one-legged cycle ergometry at 70% maximal oxygen uptake for 45 min. Biopsies were obtained from the vastus lateralis muscle 7 days before and at 1, 2, 3, and 6 days after exercise. Muscle superoxide dismutase activity increased to a peak at 3 days postexercise, muscle catalase activities were unchanged, and muscle content of HSP60 and the inducible HSP70 increased by variable amounts to reach means of 190% and 3,100% of preexercise values, respectively, by 6 days postexercise. These data indicate that human skeletal muscle responds to a single bout of nondamaging exercise by increasing superoxide dismutase activity and provide the first evidence of an increase in HSP content of human skeletal muscle after a submaximal exercise bout.

scholarly journals The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle

2015 ◽  
Vol 309 (8) ◽  
pp. L857-L871 ◽  
Author(s):  
Shelly R. H. Pecorella ◽  
Jennifer V. F. Potter ◽  
Anne D. Cherry ◽  
Dionne F. Peacher ◽  
Karen E. Welty-Wolf ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Glucose Transporter ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Heme Oxygenase 1 ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Mitochondrial Density ◽  
Muscle Plasticity

The heme oxygenase-1 (HO-1)/carbon monoxide (CO) system induces mitochondrial biogenesis, but its biological impact in human skeletal muscle is uncertain. The enzyme system generates CO, which stimulates mitochondrial proliferation in normal muscle. Here we examined whether CO breathing can be used to produce a coordinated metabolic and vascular response in human skeletal muscle. In 19 healthy subjects, we performed vastus lateralis muscle biopsies and tested one-legged maximal O2 uptake (V̇o2max) before and after breathing air or CO (200 ppm) for 1 h daily for 5 days. In response to CO, there was robust HO-1 induction along with increased mRNA levels for nuclear-encoded mitochondrial transcription factor A (Tfam), cytochrome c, cytochrome oxidase subunit IV (COX IV), and mitochondrial-encoded COX I and NADH dehydrogenase subunit 1 (NDI). CO breathing did not increase V̇o2max (1.96 ± 0.51 pre-CO, 1.87 ± 0.50 post-CO l/min; P = not significant) but did increase muscle citrate synthase, mitochondrial density (139.0 ± 34.9 pre-CO, 219.0 ± 36.2 post-CO; no. of mitochondrial profiles/field), myoglobin content and glucose transporter (GLUT4) protein level and led to GLUT4 localization to the myocyte membrane, all consistent with expansion of the tissue O2 transport system. These responses were attended by increased cluster of differentiation 31 (CD31)-positive muscle capillaries (1.78 ± 0.16 pre-CO, 2.37 ± 0.59 post-CO; capillaries/muscle fiber), implying the enrichment of microvascular O2 reserve. The findings support that induction of the HO-1/CO system by CO not only improves muscle mitochondrial density, but regulates myoglobin content, GLUT4 localization, and capillarity in accordance with current concepts of skeletal muscle plasticity.

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